Is CPLANE1 p.Pro375= (c.1125A>G) pathogenic?

CPLANE1 p.Pro375= (c.1125A>G) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.85%, afr); Associated with Joubert syndrome 17.

What condition is associated with CPLANE1 p.Pro375= (c.1125A>G)?

CPLANE1 p.Pro375= (c.1125A>G) is associated with Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Pro375= (c.1125A>G) in the general population?

CPLANE1 p.Pro375= (c.1125A>G) is low-frequency (popmax 4.85%, afr) (gnomAD).

CPLANE1 p.Pro375=

c.1125A>G · rs61745362 · VCV158026

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.85%, afr)

Conditions

Joubert syndrome 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.18	GERP 0.36, phastCons 0.71
Overall
CADD	7.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.85% African / African-American · 3,540/73,062 alleles

Filtering AF 4.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.66%

Overall 0.26% 4,032/1,549,232 alleles · low-frequency exomes 1,981/1,396,956 · genomes 2,051/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.85%	21
Remaining individualsnot grpmax-eligible	0.34%	294
Admixed American	0.276%	363
Middle Eastern	0.201%	498
European (non-Finnish)	0.0111%	9,023
South Asian	0.00954%	10,480
East Asian	0.00245%	40,844

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CPLANE1
Protein: p.Pro375=
Coding: c.1125A>G
MANE Select: NM_001384732
dbSNP: rs61745362
Type: single nucleotide variant
Location: chr5:37227814 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 p.Pro375Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CPLANE1 p.Pro375Leu Uncertain significance ★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cplane1-p-pro375 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown